Side Effect Management Flashcards
Akathisia
Characteristics: Sense of restlessness (often internal without obvious movement); patient fidgety, pacing, “crawling” or “shocks” under the skin, and has difficulty sitting still; can lead to agitation and even SI; develops usually within a few hours of a dose, but may take weeks to develop as well.
Offending Meds: antipsychotics (esp. high-potency); occasionally SRIs and buspirone
Mechanism: D2 blockage
General Management: a) reduce dose; b) switch agent (to atypical or lower potency)
First-Line Meds: a) propranolol (10mg BID to 90mg/d) or Inderal (60-90mg daily); b) benzodiazepine (start at 10mg diazepam equivalent)
Second-Line Meds: a) benztropine 1mg BID); b) cyprohepadine 8-16mg daily; c) amantadine 100-250mg BID; d) clonidine 0.2mg-0.8mg daily; e) gabapentin 1200mg daily; f) trazodone 100mg/d; g) mirtazapine 15mg/d
Clinical Pearls: a) clozapine, quetiapine, and lurasidone have no higher rates than placebo; b) may form in a tardive form with symptoms lasting for greater than six months
Fun Facts: comes from Greek (a-kathis meaning no sitting) and the word cathedral is from the same word (cathedral is a church of the bishop’s seat)
Bruxism
Characteristics: involuntary grinding of teeth (esp. during sleep); can cause tooth destruction, TMJ, myofascial pain, and sleep disturbance in 5% of patients
Offending Meds: SRIs; SNRIs; stimulants; antipsychotics; illicit drugs (cocaine, meth, ecstasy)
Mechanism: unclear, but related to central dopaminergic and serotonergic systems
General Management: a) reduce dose or switch medication; b) wear dental guards at night; c) treat anxiety (which worsens bruxism); d) stop/decrease smoking; e) watchful waiting often sees a remission in about a month
First-Line Meds: buspirone 10mg BID to TID
Second-Line Meds: a) clonazepam 0.5mg to 1mg QHS; b) gabapentin 300mg QHS; c) Bo-tox into the masseter for persistent symptoms
Clinical Pearls: risk factors include OSA, parasomnias, and heavy alcohol use
Fun Facts: People with bruxism are referred to as “bruxers” or “bruxists”
Constipation
Characteristics: Straining to have bowel movements; hard stools; sense of incomplete evacuation
Offending Meds: antipsychotics (esp. clozapine and olanzapine); SRIs (esp. paroxetine); SNRIs; mirtazapine; TCAs; benztropine; antihistamines; opiates
Mechanism: decrease in bowel motility due to anticholinergic effects
General Management: a) decrease dose; b) increase fluids; c) increase dietary fiber; d) increase physical activity; e) prunes (crossover trial says it works better than psyllium in frequency and consistency)
First-Line Meds: a) Bulk-forming laxatives (psyllium (Metamucil) or methylcellulose (Citrucel) 1T TID); b) Stool softeners (docusate (Colace) 100-250mg BID)
Second-Line Meds: a) osmotic laxatives (lactulose 15-30mg daily; polyethylene glycol (Miralax (8-34g in 8oz); Mg Citrate (150-300mL daily); b) stimulant laxatives (sennosides (Ex-Lax/Senokot); bisacodyl (Dulcolax); MOM (magnesium hydroxide))
Clinical Pearls: DDx includes irritable bowel syndrome (constipation alternating with diarrhea), hypothyroidism, and colon cancer (look for blood in stool and weight loss)
Xerostomia (Dry Mouth)
Characteristics: Uncomfortable sense of dryness due to diminished saliva; can lead to cavities because some saliva has an antibacterial effect; can lead to decreased taste sensation and inflammation of gums
Offending Meds: Most psychotropic medications
Mechanism: Anticholinergic effects (among others)
General Management: Encourage aggressive oral hygiene and dental cleanings; chew sugarless gum to promote saliva production (especially gum with xylitol which reduces cavities); increase water or suck on ice chips; reduce caffeine (worsens dry mouth)
First-Line Meds: a) Biotene products (gum, toothpaste, mouthwash, gels, and sprays) as they contain lubricants and humectants to “seal in moisture”; b) Saliva substitutes (e.g., Oralube or Oasis mouth spray)
Second-Line Meds: Pro-cholinergic agents (e.g., pilocarpine 5-10mg 2-3x daily; cevimeline 30mg up to TID) – do not shy from these if Biotene products not preferred by the patient.
Clinical Pearls: Aging itself is a common cause of dry mouth, so do not be quick to blame medications in the older patients.
Dystonia
Characteristics: Involuntary contractions of muscles; Can include torticollis (twisting neck), opisthotonos (arching spine or neck), oculogyric crisis (eyes rolling back), and trismus (jaw clenching). Rarely associated with tongue swelling, which can cause choking when eating.
Offending Meds: Antipsychotics, esp. high potency; rare, but possible, with atypicals
Mechanism: D2 blockage
General Management: reduce dose if possible; switch if required; consider initial prophylaxis for those in high risk or previous reactions
First-Line Meds: a) benztropine 1mg-2mg daily or twice daily; b) diphenhydramine 50mg daily; IM if severe initially, then give oral
Second-Line Meds: a) benzodiazepines (diazepam most efficacious at 5-10mg); b) amantadine 100-200mg BID (no IM form); c) trihexyphenidyl 1mg-2mg TID (no IM form); Bo-Tox (esp. cervical dystonia)
Clinical Pearls: a) males at higher risk; b) earliest signs generally occur within hours of the dose, with 90% of reactions within the first five days; c) may form in a tardive form with symptoms lasting for greater than six months
Fun Facts: dystonias have many other causes than antipsychotics and is the third most common movement disorder in the United States (following essential tremor and Parksinson’s disease
Hyperhidrosis (Excessive Sweating)
Characteristics: Excessive sweating, generally in face, neck and chest (less so in armpits or palms)
Offending Meds: Antidepressants (esp. SNRIs) and bupropion
Mechanism: Dysregulation of cholinergically-innervated sweat glands
General Management: Reduce dose or switch agents; more frequent showers
First-Line Meds: a) terazosin (alpha-1 blocker) 1mg at bedtime (to 4-6mg); b) clonidine 0.1mg daily; c) benztropine 1mg BID; d) glycopyrrolate 1mg BID up to 2mg TID (or PRN) – but this is SO effective that it can reduce the body from sweating to cool, so can cause fevers and heatstroke in higher temperature weather or exercise
Second-Line Meds: a) oxybutynin 5-10mg daily or twice daily; b) mirtazapine to 60mg daily; c) cyproheptadine 4mg daily or twice daily; d) aripiprazole 10mg daily
Clinical Pearls: risk factors include those who tended to sweat a lot before the medications; often not noticed in the winter
Fatigue
Offending Meds: antidepressants; antipsychotics; mood stabilizers; anticholinergic agents; opiates
Mechanism: generally secondary to antihistamine or anticholinergic effects
General Management: a) watchful waiting; b) change dosing to bedtime; c) reduce dose; d) consider switching to bupropion
First-Line Meds: a) modafinil 100-300mg in divided doses; b) armodafinil 150-250mg in divided doses
Second-Line Meds: psychostimulants (work to long-acting agents preferentially)
Clinical Pearls: a) r/o non-medication causes of fatigue (i.e., anemia, hypothyroidism, and OSA); b) r/o fatigue as a residual depressive symptom; c) consider number of hours worked
Nausea
Offending Meds: Serotonergic agents (esp. vortioxetine); lithium; VPA; naltrexone
Mechanism: Various; stimulation of 5HT3 receptors
General Management: a) wait through side effect weeks (often resolves); b) reduce dose; c) start drug at half dose and go up slowly in susceptible patients; d) take medications after meals/with spoon of peanut butter; e) split dosing; f) switch to delayed release; g) change to non-serotonergic agent
First-Line Meds: a) ginger root (2 caps 3x/d – 30min before meals, then take medications after meals); b) mirtazapine 15mg daily (as a 5HT3 blocker); ondansetron (Zofran) 4-8mg TID PRN (as a 5HT3 blocker);
Second-Line Meds: phenothiazine agents (Phenergan; prochlorperazine; metoclopramide)
Orthostatic Hypotension
Characteristics: Caused by blood pooling in the lower extremities when standing, causing less blood flow to the brain and consequently dizziness
Offending Meds: prazosin; antipsychotics (esp. clozapine, risperidone, quetiapine, and low potency agents); TCAs; MAOIs; trazodone; less frequently mirtazapine
Mechanism: alpha-1 blockage which tells the body to constrict blood vessels and maintain blood pressure when standing up; (also, some anticholinergic effects)
General Management: a) review for blood pressure changing medications; b) start at lower doses for higher-risk patients; c) change dosing to minimize peak blood levels; d) instruct patient to stand slowly while on these medications; e) increase fluids; f) use compression stockings for more severe cases; g) consider increase salt intake (if no HTN); h) limit alcohol use
First-Line Meds: (only for severe, refractory cases): a) fludrocortisone (Florinef) 0.1mg-0.3mg (watch for hypokalemia); b) midodrine 10mg 3x daily (watch for parethesias)
Clinical Pearls: OH is defined as a 20mm drop in systolic and/or 10mm drop in diastolic; if the symptom happens after an hour or two after the medications, it is most likely medication-induced; OH in middle age increases the risk of cognitive decline and dementia.
Parkinsonism
Characteristics: Tremor (esp. “pill-rolling”); rigidity (esp. cog-wheel); bradykinesia; decreased arm swing; shuffling gait; masked facies; drooling; bradyphrenia (cognitive dulling); worsened negative symptoms; worsened depression
Offending Meds: Antipsychotics (esp. typical agents, but known in atypicals); Least: clozapine; olanzapine; quetiapine; ziprazadone
Mechanism: D2 blockage; disruption of the balance between dopaminergic vs. cholinergic neurons
General Management: Decrease dose or change agent.
First-Line Meds: a) benztropine 1-2mg 1-2x/d; b) trihexyphenidyl 2-5mg 1-2x/d; c) diphenhydramine 50mg/d
Second-Line Meds: amantadine 100-200mg BID (enhances dopamine release)
Clinical Pearls: Usually seen about 1-2 mos after initiation; consider starting management at same times as initiation; consider d/c anticholinergic after several weeks to see if symptoms persisted.
Fun Facts: Parkinson’s Disease results from the loss of neurons in the substantia nigra, where most dopamine is produced (named for Dr. James Parkinson)
Prolactinemia
Characteristics: Elevated prolactin levels (>29ng/ml in non-lactating/pregnant women; >18ng/ml in males); In women: menstrual irregularity, amenorrhea, infertility, low libido, galactorrhea, decreased bone density; In men: gynecomastia; erectile dysfunction, low libido, infertility, galactorrhea
Offending Meds: Antipsychotics (esp. risperidone, paliperidone, and haloperidol); estrogen, metoclopramide, verapamil
Mechanism: D2 blockade
General Management: reduce dose or switch medications (e.g., aripiprazole or quetiapine). Levels normalize in 2-4 days after discontinuation
First-Line Meds: Add aripiprazole (5mg-20mg daily) if causative drug discontinuation is not feasible
Second-Line Meds: a) Add dopamine agent (cabergoline 0.25mg twice a WEEK; bromocriptine 1.25-2.5mg daily); b) OCP (but it only prevents bone loss in women and treats testosterone deficiency I men—it does NOT treat hyperprolactinemia)
Clinical Pearls: a) if levels are around 40ng/ml, recheck, but as a fasting level (levels influenced by stress); b) levels >100ng/ml are high likelihood of adenoma
Fun Facts: Other causes: hypothyroidism; pregnancy; kidney disease, polycystic ovarian syndrome; pituitary adenoma; prolactin known to modulate anxiety; elevated levels seen in new fathers.
QTc Interval Prolongation
Characteristics: The QT Interval in the cardiac cycle represents depolarization (contraction) and repolarization (relaxation) of ventricles. The QTC is the corrected interval time accounting for variations in heart rate. Normal for females is <460msec and <450msec in males. Prolongation can lead to arrythmias, torsades de pointes (TdP), and sudden death. QTc above 500mex is significant risk factor for TdP.
Offending Meds: Typical antipsychotics (esp. thioridazine, chlorpromazine, and IV haloperidol); ziprasidone (though lower rate than typicals); high-dose citalopram (>40mg); amitriptyline; maprotiline; methadone; most psychotropics in overdose
Mechanism: TCAs: blockage of sodium and calcium channels; SSRI/antipsychotics: blockage of potassium channels
General Management: a) Identify risk factors; b) get baseline electrolyes and EKG; c) monitor frequently.
Low Risk Antipsychotics: aripiprazole, asenapine, lurasidone, olanzapine, quetiapine
Low Risk Antidepressants: all are good except citalopram at >40mg; sertraline studied in cardiac patients.
Risk Factors: Long QT Syndrome; female gender; older age; electrolyte abnormalities (especially low potassium, calcium, and magnesium; watch eating disorders); high blood pressure (esp. on diuretics); hypothyroidism; hypoglycemia/diabetes; bradycardia/antiarrhythmics; pituitary insufficiency
Sexual Dysfunction
Characteristics: Includes: low libido, anorgasmia, decreased sensation, erectile dysfunction, delayed ejaculation, retrograde ejaculation
Offending Meds: antidepressants (paroxetine most common, but all can cause); antipsychotics (risperidone and paliperidone most common); some mood stabilizers (esp. valproic acid and carbamazepine)
Mechanism: Various: a) activation of 5HT2 receptors (in antidepressants); b) hyperprolactinemia (in antipsychotics); c) anticholinergic and antiadrenergic effects
General Management: a) watchful waiting; b) drug holidays (on weekends; not a good idea with paroxetine or venlafaxine because of withdrawal effects); c) decrease dose; d) switch medications
First-Line Meds: a) Saffron 15mg BID (Swanson Superior Herbs; BCN Saffron Ultra); b) SAMe 400mg BID (Doctor’s Best; Swanson High-Potency, VitaCost) c) Maca Root 3000mg daily (Nutrigold Maca Gold, Maca Magic Powder, Gaia Herbs) d) PDE5 inhibitors (sildenafil (Viagra) or tadalafil (Cialis) for ED or low libido – not so effective in women); e) add bupropion (more effective in women than men); f) mirtazapine 15-45mg daily
Second-Line Meds: a) buspirone 30-60mg daily; b) periactin 8mg before sexual activity; c) amantadine 100mg daily
Clinical Pearls: Take a sexual history for the sexual ADEs before starting medications
Fun Facts: Early reports from Pharma reported incidence from 2-16%, but prospective studies have now found the incidence closer to 58-73%.
Sialorrhea (Hypersalivation)
Characteristics: Excessive drooling, usually more severe at night.
Offending Meds: Clozapine (30-80% incidence); also, in olanzapine, risperidone, and quetiapine
Mechanism: Pro-cholinergic effects
General Management: a) towel on pillow; b) chewing sugar-free gum to promote swallowing
First-Line Meds: glycopyrrolate (Robinul): 1mg at bedtime, increasing to 1-2mg BID if daytime symptoms (does not cross BBB, so there are fewer anticholinergic side effects)
Second-Line Meds: Natural Treatments: a) chewing cloves; b) drinking cinnamon tea; Medicationa) ipratropium (Atrovent) 0.03% nasal spray (1-2 sprays SL); b) oxybutynin (Ditropan) 5mg BID; c) clonidine 0.1mg daily (or guanfacine); d) benztropine (Cogentin) 1mg BID; e) trihexyphenidyl (Artane) 5mg BID; f) atropine 1% ophthalmic drops 1 drop TID SL
Clinical Pearls: Dose reduction does not tend to diminish symptoms; clozapine has STRONG anticholinergic properties, so the pro-cholinergic effect here is puzzling—theories have included specific stimulation of cholinergic salivary receptors or impairment in the autonomically-mediated swallowing mechanism (which contributes to the clozapine-related dysphagia and pneumonia)
Tardive Dyskinesia
Characteristics: Involuntary movements usually involving oro-buccal-lingual (chewing, lip smacking, and tongue protrusion). Occasionally movements involve toes and fingers.
Offending Meds: First generation antipsychotics primarily (3-5% per year); risk is smaller in SGAs (risperidone carries highest risk)
Mechanism: D2 blockage leading to dopamine receptor hypersensitivity
General Management: a) Identify patients with risk factors (high-potency agents; higher doses; elderly; African American populations); b) Monitor patients with AIMS; c) Switch to SGA or other antipsychotic
First-Line Meds: a) valbenazine (Ingrezza) 40mg daily increasing to 80mg after a week; b) deutrebenazine (Austedo) 6mg BID, increasing by 6mg weekly to max of 48mg/d
Second-Line Meds: a) amantadine 100-300mg daily; b) Gingko biloba240mg/d; c) Vitamin E 400-600 IU per day; d) clonazepam 0.5-1mg daily or BID
Clinical Pearls: a) increasing doses looks like it improves the symptoms, but they get worse long-term; b) lowering the dose worsens the symptoms (“withdrawal dyskinesia”) initially (or even unmasks TD not observed before); c) metoclopramide (Reglan) and prochlorperazine (Compazine) are also large TD offenders.
